Studies were continued on the metabolic disposition of misonidazole (NSC-261037), desmethylmisonidazole (NSC-261036), and m-AMSA (NSC-249992). The O-demethylation conversion of misonidazole to desmethylmisonidazole by rat liver microsomes was characterized. An isolated rat liver perfusion system was used to study the dose-dependent elimination kinetics of misonidazole and desmethylmisonidazole. Studies on the clinical pharmacokinetics of desmethylmisonidazole were initiated in conjunction with the Phase I clinical evaluation of this agent. Conditions for the in vitro microsomal metabolism of m-AMSA were established. Studies on the oral absorption and enterohepatic recirculation of m-AMSA were completed. The distribution of m-ASMA in the CSF of monkeys was determined following intraventricular administration and by lumbar puncture.